PROJECT SUMMARY Although male mosquitoes are obligate carbohydrate feeders, female mosquitoes that transmit pathogens to humans feed on nectar as well as blood, which is required to complete cycles of egg development. Carbohydrate and blood meals are dispatched to different compartments of the digestive tract. Sugars enter the crop, a specialized foregut organ in the Diptera, access to which is controlled by a sphincter valve. Blood meals, on the other hand, are directed to the midgut, which is equipped with specialized structures such as the peritrophic membrane to protect the mosquito from effects of pathogens and imbalances from chemical constituents of the blood, as well as to aid digestion. Previous investigations of mechanisms that underlie ?switching? of meal destination in various dipterans implicate physical factors such as meal temperature and osmotic pressure, as well as the chemical nature of the meal. However, the literature describes a lot of variability across species, and this problem has not received much attention for the past couple of decades. We have conducted preliminary experiments to first establish the robustness of the switching mechanism in the Aedes aegypti mosquito, and to test the involvement of physical and chemical factors in affecting meal destination. We use these results to set up conditions that disrupt meal destination, and determine the consequences of diverting a blood meal to both the crop and midgut on fecundity. Based on our results, our hypothesis is that in A. aegypti, the crop valve opens for a carbohydrate meal but remains closed for a blood meal, which thus ends up in the midgut. Furthermore, our findings show that shunting blood to the crop yields a dramatic reduction in the number of blood-fed females that lay eggs as well as the number of eggs laid by individual females. Our overall goals are to build upon these initial findings to investigate meal factors and sensory mechanisms that underlie the meal destination switching mechanism. Our experimental approach will be 1) to further characterize the biological importance of the switching mechanism, 2) to identify meal properties (physical and chemical) that influence meal destination, and 3) to test the roles of candidate genes, selected by the elucidation of critical meal properties, in controlling meal destination. Completion of the proposed experiments will provide an understanding of fundamental principles of feeding and digestive tract function that may be shared across many hematophagous insects that spread deadly diseases.